Relative Cost-effectiveness Of Using An Extensively Hydrolyzed Casein Formula In Managing Infants With Cow's Milk Allergy In Brazil

To estimate the cost-effectiveness of three alternative dietetic strategies for cow's milk allergy in Brazil: 1) using an extensively hydrolyzed casein formula (eHCF; -Nutramigen) as a first-line formula, but switching to an amino acid formula (AAF) if infants remain symptomatic; 2) using an AAF as a first-line formula and then switching to an eHCF after 4 weeks once infants are symptom-free, but switching back to an AAF if infants become symptomatic; and 3) using an AAF as a first-line formula and keeping all infants on that formula. The analysis was conducted from the perspective of the Brazilian public health care system, Sistema Unico de Saude. Methods: Decision modeling was used to estimate the probability of immunoglobulin E (IgE)-mediated and non-IgE-mediated allergic infants developing tolerance to cow's milk by 12 months from starting a formula. The models also estimated the Sistema Unico de Saude cost (at 2013/2014 prices) of managing infants over 12 months after starting a formula, as well as the relative cost-effectiveness of each of the dietetic strategies. Results: The probability of developing tolerance to cow's milk by 12 months from starting a formula was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were initially fed with an eHCF, compared with those who were initially fed with an AAF. The total health care cost of initially feeding an eHCF to cow's milk allergic infants was less than that of initially feeding both IgE-mediated and non-IgE-mediated infants with an AAF. Conclusion: Within the study's limitations, using an eHCF instead of an AAF for the first-line management of newly-diagnosed infants with cow's milk allergy affords a cost-effective use of publicly funded resources, since it improves the outcome for less cost.8629639Mead Johnson Nutrition, Sao Paulo, Brazi

Relative cost-effectiveness of using a liquid human milk fortifier in preterm infants in the US

Objective: To estimate the cost-effectiveness of using a liquid human milk fortifier (LHMF) compared to a powdered human milk fortifier (PHMF) in preterm infants in the US from the perspective of third-party payers and parents. Methods: This was a decision modelling study using patient data obtained from a random- ized controlled trial comparing a LHMF with a PHMF in preterm infants, supplemented with additional data obtained by performing a chart review among 79% of the trial patients. The model estimated the cost-effectiveness of LHMF versus PHMF in US$at 2014/2015 prices. Results: More infants in the LHMF group were discharged home (92$10,497 per infant less in the LHMF group than the PHMF group ($240,928 versus$251,425). Conclusion: Using LHMF instead of PHMF in preterm infants enabled resources to be freed-up for alternative use within the system. There is no health economic reason why LHMF should not be used in preference to PHMF in the NICU

Modelling the annual NHS costs and outcomes attributable to healthcare-associated infections in England

Objectives To estimate the annual health economic impact of healthcare-associated infections (HCAIs) to the National Health Service (NHS) in England. Design A modelling study based on a combination of published data and clinical practice. Setting NHS hospitals in England. Primary and secondary outcome measures Annual number of HCAIs, additional NHS cost, number of occupied hospital bed days and number of days front-line healthcare professionals (HCPs) are absent from work. Results In 2016/2017, there were an estimated 653 000 HCAIs among the 13.8 million adult inpatients in NHS general and teaching hospitals in England, of which 22 800 patients died as a result of their infection. Additionally, there were an estimated 13 900 HCAIs among 810 000 front-line HCPs in the year. These infections were estimated to account for a total of 5.6 million occupied hospital bed days and 62 500 days of absenteeism among front-line HCPs. In 2016/2017, HCAIs were estimated to have cost the NHS an estimated £2.1 billion, of which 99.8% was attributable to patient management and 0.2% was the additional cost of replacing absent front-line HCPs with bank or agency staff for a period of time. When the framework of the model was expanded to include all NHS hospitals in England (by adding specialist hospitals), there were an estimated 834 000 HCAIs in 2016/2017 costing the NHS £2.7 billion, and accounting for 28 500 patient deaths, 7.1 million occupied hospital bed days (equivalent to 21% of the annual number of all bed days across all NHS hospitals in England) and 79 700 days of absenteeism among front-line HCPs. Conclusion This study should provide updated estimates with which to inform policy and budgetary decisions pertaining to preventing and managing these infections. Clinical and economic benefits could accrue from an increased awareness of the impact that HCAIs impose on patients, the NHS and society as a whole

Genomic insights into the mechanism of carbapenem resistance dissemination in Enterobacterales from a tertiary public heath setting in South Asia

Background Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 to September 2017. Methods We enrolled patients and collected epidemiology and outcome data. All Enterobacterales were characterised phenotypically and by whole genome sequencing. Risk assessment for the patients with CRE were performed compared to patients with carbapenem-susceptible Enterobacterales (CSE). Results 10.6% of all 1831 patients with a clinical specimen collected had CRE. In-hospital 30-day mortality was significantly higher with CRE [50/180 (27.8%)] than CSE [42/312 (13.5%)] (p = 0.001); however, for blood-stream infections, this was insignificant. Out of 643 Enterobacterales isolated, 210 were CRE. blaNDM was present in 180 isolates, blaOXA-232 in 26, blaOXA-181 in 24 and blaKPC-2 in 5. Despite this, ceftriaxone was the most commonly prescribed empirical antibiotic and only 27% patients were prescribed at least one antibiotic to which their infecting pathogen was susceptible. Significant risk factors for CRE isolation included burns unit and ICU admission, and prior exposure to levofloxacin, amikacin, clindamycin and meropenem. E. coli ST167 was the dominant CRE clone. Clustering suggested clonal transmission of K. pneumoniae ST15 and the MDR hyper-virulent clone, ST23. The major trajectories involved in horizontal gene transfer were IncFII and IncX3, IS26, and Tn3. Conclusion This is the largest study from a SA public hospital combining outcome, microbiology and genomics. The findings indicate the urgent implementation of targeted diagnostics, appropriate antibiotic use and infection control interventions in SA public institutions

Combinations of single-top-quark production cross-section measurements and vertical bar f(LV)V(tb)vertical bar determinations at root s=7 and 8 TeV with the ATLAS and CMS experiments

This paper presents the combinations of single-top-quark production cross-section measurements by the ATLAS and CMS Collaborations, using data from LHC proton-proton collisions at = 7 and 8 TeV corresponding to integrated luminosities of 1.17 to 5.1 fb(-1) at = 7 TeV and 12.2 to 20.3 fb(-1) at = 8 TeV. These combinations are performed per centre-of-mass energy and for each production mode: t-channel, tW, and s-channel. The combined t-channel cross-sections are 67.5 +/- 5.7 pb and 87.7 +/- 5.8 pb at = 7 and 8 TeV respectively. The combined tW cross-sections are 16.3 +/- 4.1 pb and 23.1 +/- 3.6 pb at = 7 and 8 TeV respectively. For the s-channel cross-section, the combination yields 4.9 +/- 1.4 pb at = 8 TeV. The square of the magnitude of the CKM matrix element V-tb multiplied by a form factor f(LV) is determined for each production mode and centre-of-mass energy, using the ratio of the measured cross-section to its theoretical prediction. It is assumed that the top-quark-related CKM matrix elements obey the relation |V-td|, |V-ts| << |V-tb|. All the |f(LV)V(tb)|(2) determinations, extracted from individual ratios at = 7 and 8 TeV, are combined, resulting in |f(LV)V(tb)| = 1.02 +/- 0.04 (meas.) +/- 0.02 (theo.). All combined measurements are consistent with their corresponding Standard Model predictions.Peer reviewe

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement